ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021
ACT-1004-1239, a first-in-class CXCR7 antagonist with both immunomodulatory and promyelinating effects for the treatment of inflammatory demyelinating diseases.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Neurofilament Light Chain (Nfl) Level in Serum as a Suitable In Vivo Biomaker for Axonal Damage in a Murine Viral Model of Multiple Sclerosis.Journal of cellular and molecular medicine · 2026Article
- Pharmacological modulation of CXCL12/CXCR4/ACKR3 for brain disorders - an overview.Cell communication and signaling : CCS · 2026Review
- The Gut-Brain-Immune Axis in Glioma: Emerging Mechanisms and Therapeutic Opportunities.Cellular and molecular neurobiology · 2026Review
- Constitutive activity of an atypical chemokine receptor revealed by inverse agonistic nanobodies.Nature communications · 2025Article
- Inhibition of constitutive activity of the atypical chemokine receptor 3 by the small-molecule inverse agonist VUF16840.Molecular pharmacology · 2025Article
- Research Progress on Th17/Treg Cell Imbalance in Epileptic Seizures.Journal of inflammation research · 2025Review
- Chemokines as therapeutic targets for multiple sclerosis: a spatial and chronological perspective.Frontiers in immunology · 2025Review
- Constitutive activity of an atypical chemokine receptor revealed by inverse agonistic nanobodies.bioRxiv : the preprint server for biology · 2024Article
- ACKR3 Antagonism Enhances the Repair of Demyelinated Lesions Through Both Immunomodulatory and Remyelinating Effects.Neurochemical research · 2024Article
- Conformational dynamics underlying atypical chemokine receptor 3 activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The effect of itraconazole, a strong CYP3A4 inhibitor, on the pharmacokinetics of the first-in-class ACKR3/CXCR7 antagonist, ACT-1004-1239.Clinical and translational science · 2024Article
- The Role of Atypical Chemokine Receptors in Neuroinflammation and Neurodegenerative Disorders.International journal of molecular sciences · 2023Review
- Regulation of the Hippo/YAP axis by CXCR7 in the tumorigenesis of gastric cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications.International journal of biological sciences · 2023Review
- New pairings and deorphanization among the atypical chemokine receptor family - physiological and clinical relevance.Frontiers in immunology · 2023Review
- Remyelination in Multiple Sclerosis: Findings in the Cuprizone Model.International journal of molecular sciences · 2022Review
- Effects of Small Molecule Ligands on ACKR3 Receptors.Molecular pharmacology · 2022Article
- Breaking the barriers to remyelination in multiple sclerosis.Current opinion in pharmacology · 2022Review
- Plasma neurofilament light, glial fibrillary acidic protein and lysosphingolipid biomarkers for pharmacodynamics and disease monitoring of GM2 and GM1 gangliosidoses patients.Molecular genetics and metabolism reports · 2022Article
- Absorption, Metabolism, and Excretion of ACT-1004-1239, a First-In-Class CXCR7 Antagonist:Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current strategies for the treatment of demyelinating diseases such as multiple sclerosis (MS) are based on anti-inflammatory or immunomodulatory drugs. Those drugs have the potential to reduce the frequency of new lesions but do not directly promote remyelination in the damaged central nervous system (CNS). Targeting CXCR7 (ACKR3) has been postulated as a potential therapeutic approach in demyelinating diseases, leading to both immunomodulation by reducing leukocyte infiltrates and promyelination by enhancing myelin repair. ACT-1004-1239 is a potent, selective, insurmountable, and orally available first-in-class CXCR7 receptor antagonist. The effect of ACT-1004-1239 was evaluated in the myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) and the cuprizone-induced demyelination mouse models. In addition, ACT-1004-1239 was assessed in a rat oligodendrocyte precursor cell (OPC) differentiation assay in vitro. In the MOG-induced EAE model, ACT-1004-1239 treatment (10-100 mg/kg, twice daily, orally) showed a significant dose-dependent reduction in disease clinical scores, resulting in increased survival. At the highest dose tested (100 mg/kg, twice daily), ACT-1004-1239 delayed disease onset and significantly reduced immune cell infiltrates into the CNS and plasma neurofilament light chain concentration. Treatment with ACT-1004-1239 dose-dependently increased plasma CXCL12 concentration, which correlated with a reduction of the cumulative disease score. Furthermore, in the cuprizone model, ACT-1004-1239 treatment significantly increased the number of mature myelinating oligodendrocytes and enhanced myelination in vivo. In vitro, ACT-1004-1239 promoted the maturation of OPCs into myelinating oligodendrocytes. These results provide evidence that ACT-1004-1239 both reduces neuroinflammation and enhances myelin repair substantiating the rationale to explore its therapeutic potential in a clinical setting.
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Registered trials
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